Field of the Invention
The present invention relates to diagnostic and therapeutic compositions, methods of their use, and processes of their preparation.
More particularly, the invention relates to:
a) Magnetic resonance diagnostic compositions for visualization of tissues that over-express folate binding protein, comprising ligands chelated to superparamagnetic or paramagnetic metals and coupled to folate-receptor binding ligands; PA1 b) Radiodiagnostic compositions for visualization of tissues, comprising ligands chelated to radioactive gamma-emitting metals and coupled to folate-receptor binding ligands; PA1 c) Compositions for radiotherapy or for neutron capture therapy, comprising ligands chelated to radioactive alpha or beta-emitting metals or to metals suitable for neutron capture therapy and coupled to folate-receptor binding ligands; and PA1 d) Compositions for chemotherapy, comprising certain derivatives of folic acid coupled to a cancer chemotherapy drug through the alpha carboxylate of folic acid or coupled through both the alpha and gamma carboxylates. PA1 macrocyclic and non- macrocyclic ligands chelated to radioactive gamma-emitting metals and coupled to folate-receptor binding ligands through either the alpha, or both the alpha and gamma carboxylate of the folate-receptor binding ligand; and PA1 selected macrocyclic and non- macrocyclic ligands chelated to radioactive gamma-emitting metals and coupled to folate-receptor binding ligands through the gamma carboxylate of the folate-receptor binding ligand. Both derivatives of folic acid and methotrexate (MIX) are included for use in the composition. PA1 macrocyclic and non-macrocyclic ligands chelated to radioactive alpha or beta-emitting metals that are coupled to folic acid receptor binding ligands through the alpha carboxylate or through both the alpha and gamma carboxylate of the folate-receptor binding ligand, and PA1 selected ligands chelated to radioactive alpha or beta-emitting metals and coupled to folate-receptor binding ligands through the gamma carboxylate of the folate-receptor binding ligand. Both derivatives of folic acid and of methotrexate (MTX) are included for use in the composition.